1.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
2.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
3.Surgical strategies of contracted nose correction
Weiliang ZENG ; Xiancheng WANG ; Yang SUN ; Xiang XIONG ; Xianxi MENG ; Wenbo LI ; Zhongjie YI ; Zhihua QIAO
Chinese Journal of Plastic Surgery 2025;41(8):781-788
Objective:To evaluate the treatment strategies and outcomes for contracted nasal deformity.Methods:A retrospective review was conducted of the patients with contracted noses who underwent surgery at the Department of Plastic and Aesthetic Surgery, the Second Xiangya Hospital of Central South University, between January 2021 and January 2024. Based on the pathologic-anatomic features and severity of the deformity, patients were categorized as having mild, moderate or severe contraction. Mild cases received extensive subcutaneous dissection and framework reconstruction with various grafts. Moderate cases underwent preoperative nasal-skin distraction and intra-operative reconstruction with lower lateral or septal cartilage. Severe cases, in addition to reconstruction of the lower lateral cartilage and nasal septum, underwent individualized repair, including mucosal or cutaneous defect resurfacing. Postoperative follow-up assessed nasal appearance, complications and recurrence of contraction. Nasal aesthetics were quantified with visual analogue scale (VAS, 0-10 points; higher scores = less deformity), and patient satisfaction with the rhinoplasty outcome evaluation (ROE) questionnaire (0 = very dissatisfied, 100 = very satisfied) before surgery and at final follow-up. Paired t-test was used for VAS and ROE comparisons; categorical variables were analyzed with the χ2 test. A P-value < 0.05 denoted statistical significance. Results:A total of 96 patients were included, comprising 7 males and 89 females, aged (27.4 ± 8.0) years (19-58 years). There were 64 cases of mild, 19 cases of moderate, and 13 cases of severe contracted nose deformities. Postoperative follow-up(14.0 ± 4.6) months (6-19 months). No cases of abnormal nasal appearance, infection, necrosis, scar hyperplasia, or recurrence of contracted nose were observed during follow-up. Significant improvements in nasal aesthetic outcomes were observed. The VAS scores for mild, moderate, and severe contracted noses increased significantly from preoperative values of 4.7 ± 1.0, 3.0 ± 1.2, and 2.2± 1.1 to postoperative values of 8.6 ± 0.7, 8.9 ± 0.7, and 8.2 ± 0.9, respectively (all P < 0.01). Similarly, the ROE scores improved significantly from 59.1 ± 10.0, 34.2 ± 12.1, and 28.5± 6.3 preoperatively to 90.2 ± 9.5, 91.5 ± 7.5, and 93.3 ± 5.8 postoperatively (all P < 0.01). Conclusion:Selecting appropriate surgical methods based on the pathological and anatomical characteristics and severity of contracted nose deformities can achieve favorable outcomes. Postoperative nasal aesthetic appearance is significantly improved, and patient satisfaction is high.
4.Advances in multi-source surveillance data integration and application of early warning indicators for respiratory infectious diseases
Dazhu HUO ; Ting ZHANG ; Jinzhao CUI ; Xiaochen ZHANG ; Yongtao CHI ; Yanan WANG ; Zhe WANG ; Xin ZHAO ; Ziliang FAN ; Chuchu YE ; Chuangsen FANG ; Yanming LI ; Zhongjie LI ; Weizhong YANG ; Chen WANG
Chinese Journal of Preventive Medicine 2025;59(8):1311-1319
The integration of multi-source data and the establishment of early warning indicator systems constitute pivotal elements for advancing surveillance and early warning capacities in respiratory infectious diseases. Given the multifaceted transmission mechanisms and complex contributing factors inherent in respiratory infectious diseases, surveillance datasets and associated early warning indicators demonstrate notable heterogeneity and sophisticated interrelationships. Furthermore, as surveillance and early warning requirements significantly vary across diverse epidemiological scenarios, accurate assessment of the value and applicability of distinct data types and indicators is imperative. This paper systematically reviews and synthesizes recent advancements in surveillance data and early warning indicators for respiratory infectious diseases, drawing on both domestic and international research. Particular attention is dedicated to analyzing the applicability and efficacy of various data types and indicators within multiple practical contexts, aiming to provide robust theoretical frameworks and methodological guidance to facilitate the development of resilient and efficient surveillance and early warning systems for respiratory infectious diseases.
5.Incidence and Mortality of Colorectal Cancer in Zhejiang Cancer Registration Areas in 2021 and Trends from 2000 to 2021
Yunfeng ZHU ; Yi ZHOU ; Tianjing GAO ; Enning LU ; Xiaofei CHEN ; Zhongjie ZHU ; Weimiao WU ; Huizhang LI ; Lingbin DU ; Chunxiao JIANG ; Yanfei QIU
China Cancer 2025;34(10):783-791
[Purpose]To analyze the incidence and mortality of colorectal cancer in Zhejiang can-cer registration areas in 2021 and its temporal trends from 2000 to 2021.[Methods]Data from 22 cancer registries in Zhejiang Province in 2021 that met the quality standards were included.The crude incidence/mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC/ASMRC)and by world standard population(ASIRW/ASMRW),and cumulative incidence(mortality)rate for 0~74 years old were calculated.Trends from 2000 to 2021 were ana-lyzed using the Joinpoint regression model by calculating the annual percentage change(APC)and average annual percentage change(AAPC).[Results]In 2021,the number of new colorectal cancer cases in Zhejiang cancer registration areas was 12 265,with 4 323 deaths.ASIRC and ASMRC were significantly higher in men(32.74/105 and 10.11/105)than those in women(20.78/105 and 5.99/105).Urban areas showed higher ASIRC and ASMRC(28.27/105 and 8.06/105)than rural areas(24.12/105 and 7.85/105).The age-specific incidence and mortality rates of colorectal cancer in Zhejiang Province showed an increasing trend with age,with a peak of 219.63/105 in the age group of 80~84 years old.The age-specific mortality rate peaked in the age group of 85 years old and above,with a peak of 199.65/105.From 2000 to 2021,ASIRC in Zhejiang Province showed an upward trend(AAPC=2.23%,P<0.001),ASMRC showed a marginal increase(AAPC=0.78%,P=0.067).[Conclusion]The incidence of colorectal cancer in Zhejiang Province had been on a continuous rise in the past 22 years,and health education and early screening should be empha-sized.
6.Mechanism and clinical research progress of remifentanil in the prevention and treatment of emergence agitation
Na WANG ; Yongbo DUAN ; Zhongjie XIAO ; Yujing SONG ; Wenjun YAN
China Pharmacy 2025;36(15):1947-1952
Emergence agitation(EA)is a common complication after general anesthesia,especially in children and adolescents.Remifentanil,as a short-acting μ-receptor agonist,has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression.This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA.Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network,including regulation of microglial inflammatory pathways,and the modulation of cytokines and chemokines,etc.Clinical studies have shown that remifentanil can significantly shorten the recovery time,reduce the incidence of EA,and further optimize the analgesic effect and recovery quality by combining with other drugs(such as local anesthetics,sedatives,and opioid drugs).Future research should further explore the mechanism of action of remifentanil,optimize clinical treatment strategies,and conduct large-scale clinical trials to standardize the drug use plan,while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.
7.Analysis of risk factors and construction of a prediction model for herpes zoster complicated by kidney dysfunction
Tian ZHANG ; Zhongjie REN ; Zhonghan CHEN ; Ying LI ; Ke BIAN
Chinese Journal of Primary Medicine and Pharmacy 2025;32(1):100-105
Objective:To analyze the risk factors for herpes zoster complicated by kidney dysfunction and construct a prediction model.Methods:A retrospective analysis was conducted on the clinical data of 150 patients with herpes zoster who were admitted to Hangzhou Third People's Hospital from January 2022 to December 2023. The patients were divided into two groups based on the presence of kidney dysfunction: kidney dysfunction group ( n = 30, with kidney dysfunction) and control group ( n = 120, without kidney dysfunction). The risk factors for herpes zoster complicated by kidney dysfunction were analyzed. The logistic prediction model was constructed. The effectiveness of this prediction model in predicting herpes zoster complicated by kidney dysfunction was assessed using the receiver operating characteristic curve. Results:The differences in gender, body mass index, comorbidities (hypertension and hyperlipidemia), and sites of onset between the two patient groups were not statistically significant (all P > 0.05). The average age of the kidney dysfunction group was (67.74 ± 6.71) years, which was significantly older than that in the control group [(62.32 ± 5.58) years, t = 4.56, P < 0.001]. In the kidney dysfunction group, the proportions of patients with comorbid diabetes, severe pain, large lesion area, high-dose antiviral medication use, and hemoglobin levels < 120 g/L were 46.67% (14/30), 63.33% (19/30), 56.67% (17/30), 46.67% (14/30), and 40.00% (12/30), respectively. These values were all significantly greater than those in the control group [14.17% (17/120), 34.17% (41/120), 31.67% (36/120), 19.17% (23/120), and 10.00% (12/120), χ2 = 15.46, 2.60, 2.10, 9.76, 16.07, P < 0.001, 0.002, 0.035, 0.002, < 0.001). Logistic regression analysis revealed that older age ( OR = 3.023), comorbid diabetes ( OR = 4.315), severe pain ( OR = 3.623), large lesion area ( OR = 3.481), high-dose antiviral medication use ( OR = 4.030), and hemoglobin levels < 120 g/L ( OR = 0.151) were all significant risk factors for herpes zoster complicated by kidney dysfunction (all P < 0.05). Based on these risk factors, the following logistic prediction model was developed: Logit( P) = -8.753 + 1.106 × age + 1.462 × diabetes + 1.287 × pain severity + 1.247 × lesion area + 1.394 × high-dose antiviral medication use + (-1.889) × hemoglobin. The receiver operating characteristic curve analysis indicated that the area under the curve for predicting herpes zoster complicated by kidney dysfunction was 0.904 (95% CI: 0.859-0.937), with a sensitivity of 84.62% and a specificity of 89.04%. Conclusions:The risk factors for herpes zoster complicated by kidney dysfunction include older age, comorbid diabetes, severe pain, large lesion area, high-dose antiviral medication use, and hemoglobin levels < 120 g/L. Based on these factors, the construction of a logistic prediction model can provide a reliable basis for clinical prediction of the occurrence of kidney dysfunction.
8.Efficacy of high-flux hemodialysis in the treatment of stage 5 chronic kidney disease and its effects on nutritional status
Tian ZHANG ; Zhongjie REN ; Yueda LI
Chinese Journal of Primary Medicine and Pharmacy 2025;32(8):1181-1185
Objective:To investigate the efficacy of high-flux hemodialysis in the treatment of stage 5 chronic kidney disease and its effects on nutritional status.Methods:A retrospective study was conducted on 64 patients with stage 5 chronic kidney disease who received treatment at Hangzhou Third People's Hospital from February 2023 to February 2024. These patients were divided into an observation group and a control group according to different blood purification methods, with 32 patients per group. The control group underwent conventional hemodialysis treatment, while the observation group underwent high-flux hemodialysis. Renal function, calcium and phosphorus metabolism, inflammatory factors, and nutritional indicators were compared between the two groups before and after treatment.Results:After treatment, the observation group showed significantly lower levels of serum creatinine [(238.18 ± 64.37) μmol/L] and blood urea nitrogen [(8.35 ± 1.43) μmol/L] compared with the control group [(343.12 ± 75.28) μmol/L, (10.97 ± 1.64) μmol/L, t = 5.99, 6.81, both P < 0.05]. The observation group had lower levels of calcium [(1.65 ± 0.19) mmol/L] and phosphorus [(1.54 ± 0.28) mmol/L] compared with the control group [(2.16 ± 0.23) mmol/L, (2.03 ± 0.36) mmol/L, t = 9.67, 6.08, both P < 0.05]. After treatment, the levels of C-reactive protein in the observation group [(9.72 ± 2.65) mg/L] were lower than those in the control group [(14.98 ± 3.76) mg/L, t = 6.47, P < 0.001]. However, there were no significant differences in hemoglobin, albumin, and prealbumin levels between the two groups ( t = -0.47, -0.16, -0.48, all P > 0.05). Conclusions:High-flux hemodialysis is effective in patients with stage 5 chronic kidney disease. It significantly alleviates the inflammatory state, but it has no notable effects on nutritional status. This approach merits consideration in clinical practice.
9.Sperm donation utilization rates in nonobstructive azoospermia patients under diffe-rent testicular sperm retrieval methods during assisted reproductive technology cycles
Qianxi CHEN ; Yan CHEN ; Zhongjie ZHENG ; Wenhao TANG ; Zhen LIU ; Kai HONG ; Haocheng LIN
Journal of Peking University(Health Sciences) 2025;57(4):721-726
Objective:To analyze the proportion of nonobstructive azoospermia(NOA)patients opting for sperm bank donation under different sperm retrieval methods[percutaneous testicular sperm aspiration(TESA),microdissection testicular sperm extraction(mTESE)]and its influencing factors.Methods:Retrospective data from assisted reproductive technology(ART)cycles at the Center for Reproductive Medical,Peking University Third Hospital(from January 2019 to December 2023)were collected.Data-complete ART cycles involving NOA patients and their partners(using the last treatment cycle as the endpoint)were selected.Sperm donation utilization rates were compared across retrieval methods(fresh mTESE,fresh TESA,thawed mTESE,thawed TESA).Log-linear models were used to analyze the rela-tionship between sperm retrieval method and sperm source.Results:Among the 1 730 couples,the over-all sperm donation utilization rate was 12.66%.The highest rate occurred in the fresh mTESE group(23.42%),followed by the thawed mTESE group(5.87%).The rates for the fresh TESA and thawed TESA groups were 5.22%and 0%,respectively.Log-linear analysis demonstrated that sperm retrieval method was significantly associated with sperm source(mTESE:Estimate=4.499;TESA:Estimate=2.780;P<0.001).Conclusion:The low overall sperm donation utilization rate in ART cycles may re-flect the efficacy of synchronous sperm retrieval ART.The proportion of NOA patients opting for sperm donation was influenced by the retrieval method.Compared with patients undergoing TESA,those under-going mTESE were more inclined to utilize donor sperm after retrieval failure.
10.A comparative study on the non-placement of inferior vena cava filter during interventional procedure for patients with acute deep venous thrombosis of the lower extremities complicated with severe May-Thurner syndrome
Huang CHEN ; Qihong CHEN ; Xiaojie GAO ; Zhongjie HUANG ; Jinqi HUANG
Journal of Practical Radiology 2025;41(3):474-477
Objective To explore the necessity of placing an inferior vena cava filter(IVCF)during interventional therapy for acute lower extremity deep venous thrombosis(DVT)complicated with severe May-Thurner syndrome(MTS).Methods Patients with acute left lower extremity DVT complicated with severe MTS were retrospectively selected and divided into observation group(n=36)and control group(n=36)according to whether IVCF was implanted or not.Pulmonary embolism(PE)was evaluated using compu-ted tomography pulmonary angiography(CTPA).The improvement of the affected limb signs and the occurrence of PE symptoms during treatment were observed.The presence of trapped thrombus was checked during filter removal.The PE incidence,hospitaliza-tion costs,operation time,and hospital stay were compared between the two groups.Results Both groups had a higher thrombus clearance rate after interventional surgery,and the proportion of new small branch PE was lower without significant differences between the two groups(8.3%vs 5.6%,P=1.000).The signs of the affected limbs improved significantly,and no PE-related symptoms occurred during treatment.No obvious trapped thrombus was found when the filter was removed in the control group.Compared with the control group,the observation group had significantly reduced hospitalization costs and operation time(P<0.05).Conclusion For patients with acute lower extremity DVT complicated with severe MTS,omitting IVCF placement during interventional surgery does not increase the risk of PE and can reduce operation time and hospitalization costs.


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